Pneumococcal Vaccination Linked With Reduced COVID-19 Hospitalization, Death in Inflammatory Rheumatic Diseases

Vaccination with a pneumococcal vaccine was associated with reduced hospitalization rates and occurrence of severe forms of COVID-19, including death, among patients infected with inflammatory rheumatic diseases (IRDs). These findings suggest the involvement of vaccine-induced trained immunity when shaping the body’s immune response to other infections, according to investigators of a trial published in Vaccine.¹

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Role of Vaccination in IRD

Patients with IRDs are saddled with an increased risk of infection. IRDs, which encompass dozens of health conditions that inflame joints, muscles, and connective tissues, are often autoimmune, chronic, and long-term. Common rheumatologic conditions include gout, lupus, and arthritis. Because of the nature of these conditions, a patient’s immune system may experience underlying response alterations, making them more susceptible to infections from viruses like COVID-19 and influenza and bacteria like Streptococcus pneumoniae.^1,2

Pneumococcal and influenza vaccines have made a particular impact in providing protection to individuals against severe disease. The European League Against Rheumatism (EULAR) guidelines recommend yearly influenza vaccination and pneumococcal vaccination every 5 years in patients with IRD. Unfortunately, in many areas—including France, where the current analysis is centered—patients with IRD have unacceptable levels of vaccination uptake. This is especially concerning considering the broader immunomodulator impacts of vaccines against other infectious agents in the form of vaccine-induced trained immunity.^1,3-5

Some investigators conducted inquiries into the relationship between pneumococcal and influenza vaccinations and COVID-19 outcomes; the results suggest a modest protective effect against infection with SARS-CoV-2 and severity, but conclusions were not solidified. Most critically for this population, none of the studies investigating such a phenomenon explicitly focused on patients with IRDs or assessed the role of immunosuppressive or biologic therapies.¹

Because of the importance of generating evidence of the protective effect of vaccines in immunocompromised populations, the investigators sought to ameliorate the gap in data. They conducted the first study aiming to demonstrate that the prevalence of severe forms of SARS-CoV-2 infection and deaths in vaccinated patients (either pneumococcal and/or influenza) with IRD is meaningfully different from that observed in non-vaccinated patients with IRD.¹

Pneumococcal Vaccination Offers Protective Effect Against COVID-19

The study, a longitudinal, retrospective cohort assessment, utilized administrative claims data gathered from the French National Administrative Health Care Database. Using relevant diagnostic codes from the International Classification of Diseases 10^th Revision, long-term condition status, and/or ongoing treatment status, the authors identified a cohort of adults ages 18 years and older with IRD. Conditions falling under the IRD umbrella that were observed in the cohort included rheumatoid arthritis, spondylarthritis, and psoriatic arthritis.¹

A total of 406,156 patients with IRD were included in the database. Notably, 26.5% of patients were treated with targeted drugs for their condition. The authors identified that, among the cohort, 153,814 patients (37.9%) received pneumococcal vaccinations and 164,538 (40.5%) received influenza vaccinations.¹

For patients hospitalized for COVID-19, the proportion of those vaccinated against pneumococcal disease was lower in patients hospitalized, those who experienced a severe form of disease, and those who died because of COVID-19. Interestingly, and inversely, there was a higher proportion of patients vaccinated against influenza compared with patients who were not hospitalized for COVID-19, did not present with severe forms, and did not die because of the disease. In a notable development, the risks of death, severe COVID-19, and hospitalization were heightened among patients who received 1 or both of the influenza and pneumococcal vaccinations, which the authors relate to vaccinated individuals being exposed to higher baseline disease risk.¹

A multivariate analysis was conducted to validate the results. The results from this analysis were contrary to those previously reported, as pneumococcal vaccination was associated with decreased risk of hospitalization, experiencing a severe form of COVID-19, and death, while inversely, influenza vaccination was linked with heightened risks of these complications. The authors noted that this result was unexpected, owing to several previously conducted trials suggesting a protective effect against SARS-CoV-2 infection and its complications with influenza vaccination.¹

Possible Explanations

To explain this “paradoxical result,” the investigators offered confounding factors. Primarily, the fact that patients who are most vulnerable—such as older adults and those with comorbidities—are most likely to get vaccinated. This potentially led to an overrepresentation of high-risk patients in the vaccinated group. The results indicated that patients vaccinated against influenza and/or pneumococcal disease had higher rates of comorbidities, suggesting that these patients were inherently at the highest risk for severe COVID-19 and explaining the interesting observations.¹

For pneumococcal vaccination, the results indicated a reduced risk across all relevant COVID-19 outcomes, suggesting a protective role in this context. The authors noted that patients who were on targeted treatments had higher pneumococcal vaccination rates, an interesting observation that highlights the potential of a proactive approach to mitigate the risk of infection in patients more susceptible to severe disease. Ultimately, the protective effect of pneumococcal vaccination could be explained by the sheer necessity to protect against infection with Streptococcus pneumoniae, which could exacerbate illnesses in patients with IRD.¹

“Our findings underscore the multifaceted nature of the immune response in this population and suggest a potential role of trained immunity in COVID-19 outcomes, reinforcing the place of vaccinations in the management of patients with IRD,” the investigators concluded.¹

REFERENCES

1. Auroux M, Fabacher T, Sauleau E, Arnaud L, Coury F. Pneumococcal and influenza vaccination coverage and impact on COVID-19 infection severity in patients with inflammatory rheumatic diseases: A French National Healthcare Database analysis. Vaccine. 2025;61(13):127439. doi:10.1016/j.vaccine.2025.127439

2. Roland J, Collins D, Bard S. What is inflammatory rheumatism? Healthline. Last Updated March 22, 2022. Accessed July 11, 2025. https://www.healthline.com/health/rheumatoid-arthritis/inflammatory-rheumatism#outlook

3. Furer V, Rondaan C, Heijstek MW, et al. 2019 update of EULAR recommendations for vaccination in adult patients with autoimmune inflammatory rheumatic diseases. Annals Rheumatic Disease. 2020;79(1):39-52. doi:10.1136/annrheumdis-2019-215882

4. Brocq O, Acquacalda E, Berthier F, et al. Influenza and pneumococcal vaccine coverage in 584 patients taking biological therapy for chronic inflammatory joint: A retrospective study. Joint Bone Spine. 2016;83(2):155-159. doi:10.1016/j.jbspin.2015.11.005

5. Netea MG, Joosten LAB, Latz E, et al. Trained immunity: A program of innate immune memory in health and disease. Science. 2016;352(6284). doi:10.1126/science.aaf1098